The major goal of this Project are to identify antigens characteristics of epithelial ovarian cancer (EOC) using mouse monoclonal antibodies (mAbs) and to study some aspects of the biology of ovarian epithelium and its malignant transformation. The antigens detected by the mAbs will be characterized using biochemical and molecular approaches. An important aim will be to identify mAbs that are suitable for use in clinical trials involving EOC. Among mAbs to be studied are mAb MX35 (detecting a 95,000 glycoprotein), mAbs VK-5, 6, and 7 (detecting the MUC-1 mucin epitope), mAb MW 207 (detecting folate-binding protein) and mAb VK-8 (detecting a novel EOC antigen). This Project will also test chimeric and humanized versions of an anti-blood group Le antibody for their specificity and other parameters. Another goal will be to use various mAbs to detect markers related to the progression of normal ovarian epithelium to EOC and markers suitable for the classification of ovarian tumors. Three types of antigens will be examined: 1) blood group antigens, 2) ectopeptidases, and 3) mucins. Mucins will be studied in more detail using biochemical and molecular techniques in order to understand the role played by mucins in EOC. Also, novel methods for the analysis of the carbohydrate content of glycoproteins and mucins will be developed. The accomplishment of theses goals will provide new reagents for the diagnosis and therapy of EOC and will lead to an understanding of the antigenic changes associated with the malignant transformation of normal ovarian epithelium, tumor progression, and the biological behavior of ovarian tumors.